DESCRIPTION (Adapted for the Applicant's abstract and Specific Aims.): This study will analyze class II structure/function in vivo by producing and analyzing mutant class II transgenic (tg) mouse strains. Specific Aim 1 proposes to generate appropriate tg mice to examine the role of A beta mutations on antigen presentation, the T-cell repertoire, and on autoimmunity. Specific Aim 2 will examine class II interaction with CD4 by mutating the presumptive CD4 binding site of A beta genes and generating appropriate tg mice. Specific Aim 3 will analyze class II sites involved in dimer-dimer formation in vitro in transfected L cells and in vivo in tg mice. This will be approached by introducing mutations at sites believed to be involved in dimer-dimer formation. Specific Aim 4 will focus on generating soluble class II A and E molecules for tolerance studies.